{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:13:04Z","timestamp":1790439184923,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3500102"],"award-info":[{"award-number":["2022YFC3500102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474494"],"award-info":[{"award-number":["82474494"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Team Project of the Science and Technology Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2021B004"],"award-info":[{"award-number":["CI2021B004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Environmental pollution is an important risk factor for hypertension, and bisphenol A (BPA) is a prevalent environmental contaminant. This study aimed to investigate the potential toxicity of BPA and the underlying molecular mechanisms of BPA-induced hypertension through network toxicology and molecular docking. Initially, we predicted that BPA would be cardiotoxic. We subsequently identified 51 potential targets and extracted 14 core targets of the effects of BPA on hypertension. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that these core targets were involved primarily in the estrogen signaling pathway and the calcium signaling pathway. Furthermore, molecular docking confirmed the binding capacity of BPA to these core targets, with ADRB2, ESR1, and MMP9 potentially being the key targets through which BPA influences hypertension. Our study elucidates the molecular mechanisms of BPA toxicity and its role in hypertension induction, providing a foundation for the prevention and treatment of hypertension associated with environmental BPA exposure.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf094","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:03:00Z","timestamp":1752501780000},"source":"Crossref","is-referenced-by-count":1,"title":["Network toxicology and molecular docking strategy for Analyzing the toxicity and mechanisms of Bisphenol a in hypertension"],"prefix":"10.1093","volume":"14","author":[{"given":"Wenjie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , No. 5, Beixiange Road, Xicheng District, Beijing 100053 ,","place":["China"]},{"name":"Graduate School, Beijing University of Chinese Medicine , No. 11, North Third Ring East Road, Chaoyang District, Beijing 100029 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Yankuang New Journey General Hospital , No. 560, Kuangjiandonglu Road, Zoucheng 273500, Shandong Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Computer Science, Beijing University of Posts and Telecommunications , No. 10, Xitucheng Road, Haidian District, Beijing 100876 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , No. 5, Beixiange Road, Xicheng District, Beijing 100053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-6281","authenticated-orcid":false,"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , No. 5, Beixiange Road, Xicheng District, Beijing 100053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"2025072307304648800_ref1","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants","volume":"398","author":"NCD Risk Factor Collaboration (NCD-RisC)","year":"2021","journal-title":"Lancet."},{"key":"2025072307304648800_ref2","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019","volume":"396","author":"GBD 2019 Risk Factors Collaborators","year":"2020","journal-title":"Lancet"},{"key":"2025072307304648800_ref3","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur Heart J"},{"key":"2025072307304648800_ref4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1161\/CIRCRESAHA.117.306458","article-title":"Environmental determinants of cardiovascular disease","volume":"121","author":"Bhatnagar","year":"2017","journal-title":"Circ Res"},{"key":"2025072307304648800_ref5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3389\/fpubh.2020.00379","article-title":"Use of an Exposome approach to understand the effects of exposures from the natural, built, and social environments on cardio-vascular disease onset, progression, and outcomes","volume":"8","author":"Juarez","year":"2020","journal-title":"Front Public Health"},{"key":"2025072307304648800_ref6","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.3390\/ijerph17041212","article-title":"A detailed review study on potential effects of microplastics and additives of concern on human health","volume":"17","author":"Campanale","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2025072307304648800_ref7","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1007\/s00204-024-03793-4","article-title":"Bisphenol a and its analogues: from their occurrence in foodstuffs marketed in Europe to improved monitoring strategies-a review of published literature from 2018 to 2023","volume":"98","author":"Neri","year":"2024","journal-title":"Arch Toxicol"},{"key":"2025072307304648800_ref8","doi-asserted-by":"publisher","first-page":"113639","DOI":"10.1016\/j.envpol.2019.113639","article-title":"Association of bisphenol a and its alternatives bisphenol S and F exposure with hypertension and blood pressure: a cross-sectional study in China","volume":"257","author":"Jiang","year":"2020","journal-title":"Environ Pollut"},{"key":"2025072307304648800_ref9","doi-asserted-by":"publisher","first-page":"32580","DOI":"10.1007\/s11356-021-12805-0","article-title":"Study on the correlation of bisphenol a exposure, pro-inflammatory gene expression, and C-reactive protein with potential cardiovascular disease symptoms in young adults","volume":"28","author":"Tsen","year":"2021","journal-title":"Environ Sci Pollut Res Int"},{"key":"2025072307304648800_ref10","doi-asserted-by":"publisher","first-page":"1559325815610582","DOI":"10.1177\/1559325815610582","article-title":"Molecular mechanisms of action of BPA","volume":"13","author":"Acconcia","year":"2015","journal-title":"Dose Response"},{"key":"2025072307304648800_ref11","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3390\/jox12030015","article-title":"Endocrine-disrupting effects of Bisphenol a on the cardiovascular system: a review","volume":"12","author":"Fonseca","year":"2022","journal-title":"J Xenobiot"},{"key":"2025072307304648800_ref12","doi-asserted-by":"publisher","first-page":"e35409","DOI":"10.1016\/j.heliyon.2024.e35409","article-title":"Integrating network toxicology and molecular docking to explore the toxicity of the environmental pollutant butyl hydroxyanisole: an example of induction of chronic urticaria","volume":"10","author":"Zeng","year":"2024","journal-title":"Heliyon."},{"key":"2025072307304648800_ref13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.2174\/1570163815666180219112421","article-title":"Molecular docking in formulation and development","volume":"16","author":"Kaur","year":"2019","journal-title":"Curr Drug Discov Technol"},{"key":"2025072307304648800_ref14","doi-asserted-by":"publisher","first-page":"W513","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: a webserver for the prediction of toxicity of chemicals","volume":"52","author":"Banerjee","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref15","doi-asserted-by":"publisher","first-page":"W422","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref16","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1093\/bioinformatics\/btt540","article-title":"Shaping the interaction landscape of bioactive molecules","volume":"29","author":"Gfeller","year":"2013","journal-title":"Bioinformatics."},{"key":"2025072307304648800_ref17","doi-asserted-by":"publisher","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"Hamosh","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref18","doi-asserted-by":"publisher","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards suite: from gene data mining to disease genome sequence analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr Protoc Bioinformatics"},{"key":"2025072307304648800_ref19","doi-asserted-by":"publisher","first-page":"D1465","DOI":"10.1093\/nar\/gkad751","article-title":"TTD: therapeutic target database describing target druggability information","volume":"52","author":"Zhou","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref20","doi-asserted-by":"publisher","first-page":"e0294236","DOI":"10.1371\/journal.pone.0294236","article-title":"SRplot: a free online platform for data visualization and graphing","volume":"18","author":"Tang","year":"2023","journal-title":"PLoS One"},{"key":"2025072307304648800_ref21","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref22","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025072307304648800_ref23","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J Comput Chem"},{"key":"2025072307304648800_ref24","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J Chem Inf Model"},{"key":"2025072307304648800_ref25","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J Comput Aided Mol Des"},{"key":"2025072307304648800_ref26","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.53738\/REVMED.2024.20.886.1607","article-title":"Hypertension art\u00e9rielle et m\u00e9nopause : physiopathologie et impact des traitements hormonaux [hypertension and menopause: physiopathology and impact of the hormonal therapy]","volume":"20","author":"Juillet","year":"2024","journal-title":"Rev Med Suisse"},{"key":"2025072307304648800_ref27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1161\/HYPERTENSIONAHA.110.151969","article-title":"Equine estrogens impair nitric oxide production and endothelial nitric oxide synthase transcription in human endothelial cells compared with the natural 17\u03b2-estradiol","volume":"56","author":"Novensa","year":"2010","journal-title":"Hypertension."},{"key":"2025072307304648800_ref28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.ygcen.2014.06.013","article-title":"Distinct role of estrogen receptor-alpha and beta on postmenopausal diabetes-induced vascular dysfunction","volume":"206","author":"Bansal","year":"2014","journal-title":"Gen Comp Endocrinol"},{"key":"2025072307304648800_ref29","doi-asserted-by":"publisher","first-page":"6899","DOI":"10.1007\/s11033-020-05746-3","article-title":"Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors","volume":"47","author":"Wei","year":"2020","journal-title":"Mol Biol Rep"},{"key":"2025072307304648800_ref30","doi-asserted-by":"publisher","first-page":"e25455","DOI":"10.1371\/journal.pone.0025455","article-title":"Bisphenol a and 17\u03b2-estradiol promote arrhythmia in the female heart via alteration of calcium handling","volume":"6","author":"Yan","year":"2011","journal-title":"PLoS One"},{"key":"2025072307304648800_ref31","doi-asserted-by":"publisher","first-page":"141567","DOI":"10.1016\/j.chemosphere.2024.141567","article-title":"Toxicity of low dose bisphenols in human iPSC-derived cardiomyocytes and human cardiac organoids - impact on contractile function and hypertrophy","volume":"353","author":"Ma","year":"2024","journal-title":"Chemosphere."},{"key":"2025072307304648800_ref32","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1016\/j.ajhg.2023.08.009","article-title":"Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension","volume":"110","author":"Duijvenboden","year":"2023","journal-title":"Am J Hum Genet"},{"key":"2025072307304648800_ref33","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1002\/cpt.3351","article-title":"Clinical Pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 genotypes and Beta-blocker therapy","volume":"116","author":"Duarte","year":"2024","journal-title":"Clin Pharmacol Ther"},{"key":"2025072307304648800_ref34","doi-asserted-by":"publisher","first-page":"141395","DOI":"10.1016\/j.foodchem","article-title":"Multiplex aptamer cluster detection platform and systems toxicology study for 17\u03b2-estradiol, bisphenol a, and diethylstilbestrol","volume":"463","author":"Li","year":"2024","journal-title":"Food Chem"},{"key":"2025072307304648800_ref35","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1536\/ihj.23-265","article-title":"Astragalus (Astragalus mongholicus) improves ventricular Remodeling via ESR1 downregulation RhoA\/ROCK pathway","volume":"64","author":"Dai","year":"2023","journal-title":"Int Heart J"},{"key":"2025072307304648800_ref36","doi-asserted-by":"publisher","first-page":"104060","DOI":"10.1016\/j.etap.2023.104060","article-title":"Bisphenol a exposure inhibits vascular smooth muscle cell responses: involvement of proliferation, migration, and invasion","volume":"98","author":"Kim","year":"2023","journal-title":"Environ Toxicol Pharmacol"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/4\/tfaf094\/63829077\/tfaf094.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/14\/4\/tfaf094\/63829077\/tfaf094.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:30:52Z","timestamp":1753270252000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfaf094\/8210842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfaf094","relation":{},"ISSN":["2045-4538"],"issn-type":[{"value":"2045-4538","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,7,5]]},"article-number":"tfaf094"}}